| Title: | Mediterranean diet, metabolic signature, genetic predisposition, and risk of rheumatoid arthritis: a large-scale population-based prospective cohort study |
| Journal: | American Journal of Clinical Nutrition |
| Published: | 3 Oct 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41047128/ |
| DOI: | https://doi.org/10.1016/j.ajcnut.2025.09.051 |
Publication 19293
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Abstract
BACKGROUND: Although the Mediterranean (MED) diet has been associated with reduced rheumatoid arthritis (RA) risk, the underlying metabolic mechanisms and the role of genetic susceptibility in this relationship remain unknown.</p>
OBJECTIVES: This study aims to identify a metabolic signature linked to the MED diet and examine its association with the risk of RA, while accounting for genetic predispositions.</p>
METHODS: We analyzed data from 109,565 participants in the UK Biobank. Elastic net regression was applied to generate a MED-related metabolic signature. Cox proportional hazards models were used to assess the associations among MED diet score, its derived metabolic signature, and incident RA. A polygenic risk score for RA was incorporated to evaluate joint associations and potential interactions between genetic susceptibility and MED diet score or its metabolic signature in relation to RA risk. Mediation analysis was conducted to estimate the extent to which metabolic signature mediates the MED diet-RA association.</p>
RESULTS: Over a median follow-up of 11.6 y, 1123 participants developed RA. We identified a MED diet-related metabolic signature comprising 66 metabolites. Both MED diet score and metabolic signature were inversely associated with RA risk-comparing the 90th to the 10th percentiles, hazard ratios for RA were 0.73 [95% confidence interval (CI): 0.63, 0.84] for MED diet score and 0.60 (95% CI: 0.50, 0.70) for metabolic signature. These associations remained consistent across all strata of genetic risk. Joint analyses indicated that favorable metabolic profiles may attenuate genetic predisposition to RA. Mediation analysis showed that the metabolic signature explained 22.4% (95% CI: 11.8%, 44.8%) of the MED diet-RA association.</p>
CONCLUSIONS: We identified a robust metabolic signature reflecting the metabolic response to the MED diet. This signature was inversely associated with RA risk and partially mitigated the genetic susceptibility to RA. These findings highlight the potential of metabolic signatures for enhancing dietary assessment and guiding personalized nutritional intervention.</p>
13 Keywords
- Adult
- Aged
- Arthritis, Rheumatoid
- Diet, Mediterranean
- Female
- Genetic Predisposition to Disease
- Humans
- Male
- Metabolome
- Middle Aged
- Proportional Hazards Models
- Prospective Studies
- Risk Factors
19 Authors
- Xin Song
- Xiaofeng Ma
- Bin Yang
- Di Zhang
- Yanqiu Zou
- Bowen Lei
- Rong Xiang
- Xunying Zhao
- Yang Qu
- Sirui Zheng
- Ting Yu
- Jinyu Zhou
- Tao Han
- Yangdan Zhong
- Maoyao Xia
- Lars Alfredsson
- Karin Leander
- Mengyu Fan
- Xia Jiang
1 Application
| Application ID | Title |
|---|---|
| 99713 | Using genetic and phenotypic data to understand putative causal pathways leading to major human noncommunicable diseases. |
Enabling scientific discoveries that improve human health